A persistent barrier to the cure and treatment of neurological diseases is the limited ability of the central and peripheral nervous systems to undergo neuroregeneration and repair. Recent efforts have turned to regeneration of various cell types through cellular reprogramming of native cells as a promising therapy to replenish lost or diminished cell populations in various neurological diseases. This review provides an in-depth analysis of the current viral vectors, genes of interest, and target cellular populations that have been studied, as well as the challenges and future directions of these novel therapies. Furthermore, the mechanisms by which cellular reprogramming could be optimized as treatment in neurological diseases and a review of the most recent cellular reprogramming in vitro and in vivo studies will also be discussed.

Spinal cord injury (SCI) is associated with currently irreversible consequences in several functional components of the central nervous system. Despite the severity of injury, there remains no approved treatment to restore function. However, with a growing number of preclinical studies and clinical trials, cell transplantation has gained significant potential as a treatment for SCI. Researchers have identified several cell types as potential candidates for transplantation. To optimize successful functional outcomes after transplantation, one key factor concerns generating neuronal cells with regional and subtype specificity, thus calling on the developmental transcriptome patterning of spinal cord cells. A potential source of spinal cord cells for transplantation is the generation of exogenic neuronal progenitor cells via the emerging technologies of gene editing and blastocyst complementation. This review highlights the use of cell transplantation to treat SCI in the context of relevant developmental gene expression patterns useful for producing regionally specific exogenic spinal cells via in vitro differentiation and blastocyst complementation.

Recent advances in biomedical technologies have extended the boundaries of previously established regulatory guidelines pertaining to stem cell research. These guidelines constrained the study of human pluripotent stem cells (hPSCs) and their derivatives from use under various conditions, including the introduction of hPSCs into the brains of host animals because of concerns of humanizing the brains of animal species. Other guidelines constrained the use of hPSCs in creating human-animal chimeras because of the potential contribution of human stem cells not only to the brain but also to the germline. Some regulatory guidelines forbid the growing of human embryos ex vivo beyond the stage of primitive streak development because of concerns regarding the creation of human forms of life ex vivo. At the subcellular level, there are guidelines regulating the transfer of mitochondria within human embryos. At the molecular level, there are guidelines regulating genome editing to prevent permanent genetic alterations in germline cells. These and other issues related to stem cells have been reviewed, and new research guidelines established by the International Society for Stem Cell Research (ISSCR) for its membership. Because many of the recommended changes by the ISSCR impact research being conducted by members of the American Society for Neural Therapy and Repair (ASNTR), the ASNTR established a task force to review relevant recommendations by the ISSCR to determine which new guidelines to adopt for research conducted by the ASNTR society membership. The final ASNTR recommendations are presented in this document.

Coronavirus disease 2019 (COVID-19) in adults is well characterized and associated with multisystem dysfunction. A subset of patients develop post-acute sequelae of SARS-CoV-2 infection (PASC, or long COVID), marked by persistent and fluctuating organ system abnormalities. In children, distinct clinical and pathophysiological features of COVID-19 and long COVID are increasingly recognized, though knowledge remains limited relative to adults. The exponential expansion of the COVID-19 literature has made comprehensive appraisal by individual researchers increasingly unfeasible, highlighting the need for new approaches to evidence synthesis. Large language models (LLMs) such as the Generative Pre-trained Transformer (GPT) can process vast amounts of text, offering potential utility in this domain. Earlier versions of GPT, however, have been prone to generating fabricated references or misrepresentations of primary data. To evaluate the potential of more advanced models, we systematically applied GPT-4 to summarize studies on pediatric long COVID published between January 2022 and January 2025. Articles were identified in PubMed, and full-text PDFs were retrieved from publishers. GPT-4-generated summaries were cross-checked against the results sections of the original reports to ensure accuracy before incorporation into a structured review framework. This methodology demonstrates how LLMs may augment traditional literature review by improving efficiency and coverage in rapidly evolving fields, provided that outputs are subjected to rigorous human verification.

Spinal cord injury (SCI) often results in varying degrees of motor and sensory dysfunction with limited potential for recovery. Research into in vivo astrocyte-to-neuron reprogramming has led to promising results that, if translated to SCI, could offer substantial therapeutic benefit by replenishing lost populations of neurons for functional restoration. Previous studies have shown that AAV9-mediated delivery of NeuroD1 is capable of reprogramming astrocytes into neurons in vivo after chronic SCI in rats. Here we evaluate the dose-dependent functional and neuroprotective potential of the NeuroD1 gene therapy platform for acute and subacute SCI in rats. The Cre-dependent, DIO-based AAV9-NeuroD1 gene therapy platform was administered directly into the spinal cord of female Long-Evans rats after moderate, thoracic level 8/9 contusion SCI at one of two intervention timepoints: immediately after injury (acute) or 1 week post-contusion (subacute). The viruses were administered at a titer of 10¹¹ or 10¹³ GC/mL. We demonstrate that the AAV9-NeuroD1 reprogramming platform successfully, albeit variably, transduced spinal cells that persisted up to 6 weeks post-injury. However, histological analysis revealed substantial neuronal off-targeting, suggesting a lack of astrocyte-specific targeting from the AAV9 DIO-based delivery platform. Surprisingly, we also found titer- and intervention timing-dependent effects on motor function and tissue preservation—as demonstrated by 1–2 point decrease in BBB scoring and near 50% increase in peak lesion cavitation area—when AAV9-NeuroD1 was administered immediately after SCI. While did not find any effects of the AAV9-NeuroD1 platform on sensory function or neuroinflammatory cell density, a subset of NeuroD1 signal reflected phagocytic uptake by Iba1 and CD68-expressing microglia/macrophages. These results indicate that the NeuroD1 reprogramming platform can exacerbate injury-related functional deficits when administered in the acute stage of injury, but has neuroprotective benefit on tissue preservation when administered in the subacute stage of injury. Our study demonstrates that several factors must be considered, including viral titer and intervention timing, to assess the therapeutic potential of AAV9-NeuroD1-mediated reprogramming for SCI.